Osteomalacia is a process whereby the mineralization of bone is impaired. Aluminum has been implicated as a cause of this clinical disorder, but the mechanism by which aluminum induces a defect in the mineralization of bone has yet to be established. The osteomalacia associated with aluminum deposition in bone is a disease model of particular interest because defective mineralization of bone occurs despite normal concentrations of calcium and phosphorus in serum. It is the purpose of this proposal to study the formation and mineralization of bone in the presence and absence of aluminum using in vitro tissue culture techniques. The putative actions of aluminum as an inhibitor of the synthesis of new bone collagen and as a physical-chemical inhibitor of mineralization will be evaluated. The response of bone tissues to parathyroid hormone and to 1,25 dihydroxyvitamin D will also be studied to investigate the role of alterations in the response of bone to these hormones during exposure to aluminum as potential mechanisms to explain the skeletal toxicity of aluminum. The results of the proposed studies should further our understanding of the processs of bone matrix formation and calcification and how these are altered by exposure to aluminum. Such investigations are relevant to the clinical bone disease observed in patients with chronic renal failure who currently are exposed to aluminum as part of their therapeutic regimen.